Atrial Fibrillation 2017 -2018 Quality of Life and .../media/Non-Clinical/Files-PDFs-Excel-MS-Word … · PIONEER AF-PCI (CM Gibson et. al. ) NEJM 2016;375:2423 Group 3 - D-adjusted

ACC New York, Dec 9, 2017 No Disclosures

Atrial Fibrillation 2017 - 2018Quality of Life and Preventing Stroke

The 14 Clinical Challenges

Presenter

Presentation Notes

AF - CLINICAL CHALLENGES (14) – 2017 - 2018

1. Presentation: Simplified vs Prioritized (2)

2. Etiology: Myocardial vs Electrical (2)

3. AC Rx: When / Bridge vs TE-NSR / SCI (2)

4. AF / Stent: Triple Rx vs Double Rx (2)

5. Warf. / NOACs: Efficacy vs Safety (2)

6. Not Indicated ? AC vs LAA Closure (2)

7. Screening Screening vs No Screening (2)

1. D Kotecha et. al. . EHJ. 2016;37:2851 – ANSD – RF - <AF Death2. EHJ 2016; 37:2893 - Simple

1,2). Acute & Chronic Management Of AF









TJ Bunch et. al. Eur Heart J. 2016;37:2890BW Calenda, V Fuster, V Reddy et. al. Nat Rev Cardiol 2016;13:549

1). Gross Mechanisms of AF

Alcohol

Genetics

Aging

Obesity and AF

CJ Lavie et. al. J Am Coll Cardiol 2017;70:2022

Adipose Tissue Depots Occur Throughout The Body

JJ Fuster et. al. Circ Res. 2016;118:1786

Definition of Epicardial Fat And Related Adipose Tissues

CX Wong et. al. Eur Heart J. 2017;38:1294

Bariatric Surgery and the Risk of AF

S Jamaly et. al. J Am Coll Cardiol 2016;68:2497

S Nattel et. al. Nat Rev Cardiol. 2016; 13: 575.

2) Mechanisms of AF Initiation At The Pulmonary Veins

S Nattel et. al. Nat Rev Cardiol. 2016; 13: 575. – Also Re-entry

2) Molecular Mechanisms of Focal Ectopic Firing In Paroxysmal AF

Natural History of AF

JB Guichard et. al. J Am Coll Cardiol 2017;70:756

LA Tissue Fibrosis on 3D LGE CMR Scans

JB King, N Marrouche et. al. J Am Coll Cardiol 2017;70:1311

JAMA. 2014;311(5):498

Fibrosis of the LA Wall, Blinded To The Treating Physicians:

Stage 1 (<10% ), Stage 2 (≥10%-<20%),Stage 3 (≥20%-<30%), Stage 4 (≥30%).

Risk of MACCE Utah Stage of LAG Enhancement Severity

JB King, N Marrouche et. al. J Am Coll Cardiol 2017;70:1311









1a). AC When ?- The Prevention Of Stroke .

V Fuster, JS Chinitz, Circ. 2012 ; 125: 2285Swedish AF Cohort Register (L Friberg, GYH Lip et al) Circ. 2012; 125: 2298CHA2DS2VASc: ESC Guidelines (P Kirchhof, AJ Camm et al ) 2013 - ACC / AHA / HRS 2014 A/C Prevention - Emboli >>> Bleeding, Thrombosis > Bleeding

?

Presenter

Presentation Notes

# 34: Recommendations for the prevention of stroke in patients with atrial fibrillation. The inner circle represents treatment recommendations based on the use of the CHADS2 score, as in US guidelines.1 The outer circle represents recommendations based on the CHA2DS2-VASc model, as outlined in the European guidelines,4 which advise anticoagulant therapy in a larger proportion of patients with atrial fibrillation. Bleeding risk assessment is recommended for patients at intermediate stroke risk (yellow-shaded area), with particular caution and regular patient review for those on warfarin therapy when the HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) score is ≥3. For patients at very high risk of bleeding (eg, those with malignant hypertension or prior episodes of major bleeding), conservative monitoring without treatment should be considered. OAC indicates oral anticoagulation.

1b). To Bridge & How to Bridge for DOACs/VKAs

JU Doherty, JL Januzzi et. al. J Am Coll Cardiol 2017;69:872ORBIT=AF (BA Steinberg et al.), Circulation 2015; 131:488 – Exeptions Only

2a) Predictors of Stroke Risk Incorporated in the CHA2DS2-VASc Schemes - Atrial Cardiomyopathy

JB Guichard et. al. J Am Coll Cardiol 2017;70:756

LAA Structure / Function – Stroke in NSRCardiac Imaging For Assessment

J Romero et. al. Nat Rev Cardiol. 2014;11:470ENGAGE AF (DK Gupta et al.) EHJ 2014; 35:1457 – LA Function / NSR ?ASSERT (M Brambatti, et al.) Circ. 2014; 129:2094- LV Function / NSR ?IMPACT (DT Martin et al.) EHJ; 2015; 36:1660- LV Function / NSR ?

2b). Silent Cerebral Infarcts (SCI) Cardiac Disease And Procedures

ME Hassell et. al. Nat. Rev. Cardiol. 2013;10:696F Gaita et. al. J Am Coll Cardiol 2013;62:1990 (Italy)S Kalantarian et. al. Ann Intern Med. 2014;161:650 – 15 Studies, SCI

Silent Cerebral Ischemia in AF Correlation With Cognitive Function

F Gaita et. al. J Am Coll Cardiol 2013;62:1990 (Italy)S Kalantarian et. al. Ann Intern Med. 2014;161:650 – 15 Studies, SCI

Atrial Fibrillation as a Risk Factor forCognitive Decline and Dementia

Data are drawn from the Whitehall II study, N=10,308 at study recruitment in 1985. A battery of cognitive tests was administered four time (1997-2013) to 7428 participants -414 cases of AF-, aged 45-69 years in 1997. Compared with AF-free participants, those with longer exposure to AF (5, 10, or 15 years) experienced faster cognitive decline after adjustment for sociodemographic, behavioural, and chronic diseases (P for trend=0.01). Stroke did not explain it. In adults aged 45-85 years AF is associated with accelerated cognitive decline and higher risk of dementia

A Singh-Manoux et al., European Heart Journal 2017; 38:2612

Decline In The Global Cognitive Score Function of AF

A Singh-Manoux et. al. Eur Heart J. 2017;38:2612

Mechanisms Of AF Leading To Cognitive Decline Or Dementia

HC Diener et. al. Eur Heart J. 2017;38:2619









PIONEER AF-PCI (CM Gibson et. al. ) NEJM 2016;375:2423

1,2). Preventing Bleeding in Pts with AF-PCI

Group 3 - D-adjusted vitamin K antagonist plus DAPT for 1, 6, or 12 months.Group 2 - VLD rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, 12 MoGroup 1 - LD rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 Mo

PIONEER AF-PCI (CM Gibson et. al. ) NEJM 2016;375:2423

Group 3 - D-adjusted vitamin K antagonist plus DAPT for 1, 6, or 12 months.Group 2 - VLD rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, 12 MoGroup 1 - LD rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 Mo

1,2) CV Events in Pts with AF-PCI

Long-term Treatment Of Patients On NOAC Therapy After Revascularization – Elective or ACS

H Heidbuchel et. al. Eur Heart J. 2017;38:2137









1,2). New Oral Anticoagulants - Efficacy & Safety

Dialogues in Cardiovascular Medicine 2012;17:189

x

1a). VHD Patients on Edoxaban or Warfarin in the ENGAGE AF-TIMI 48 Trial

VHD was defined as history or baseline echo evidence of at least moderate aortic/mitral regurgitation, aortic stenosis, or prior valve surgery -bioprosthesis replacement, valve repair, valvuloplasty. Patients with moderate to severe mitral stenosis or mechanical heart valves were excluded from the trial. Comparisons were made of rates of stroke/systemic embolic event (SSEE) & major bleeding. VHD increased the risk of death, major adverse CV events, and major bleeding but did not affect the relative efficacy or safety of higher-dose edoxaban versus warfarin in AF.

R De Caterina et al., J Am Coll Cardiol 2017; 69:1372CT January et. al. J. Am. Coll. Card. 2014; 64: e1 – No Dabigatran in Mechanical HV

KE Chan et. al. J Am Coll Cardiol 2016;67:2888

2a). Characteristics of Warfarin & NOAC Agents

Doses Of The Different NOACsIn The 4 Large Trials In AF Patients

HC Diener et. al. Eur Heart J. 2017;38:860

Proposed Algorithm for Oral Anticoagulant Choices in Patients With Atrial Fibrillation and Chronic Kidney Disease

YC Lau et. al. J Am Coll Cardiol 2016;68:1452 - HIT.........(?)

2b). Initiation Or Re-initiation of Oral A/C After Intracranial Haemorrhage

ESC Working Group on Thrombosis (S Halvorsen et. al.) Eur Heart J. 2017;38:1455H-C Diener et al. Eur Heart J 2017; 38: 860 – Bleeding GI Tract: In 1 Week NOAC or AC

When available, idarucizumab is likely to be the treatment of choice for patients who present with diabigatran-induced uncontrolled or life-threatening bleeding or for those who require urgent surgery or invasive procedures. Other reversal agents are in development to reverse other NOACs. These include andexanet alfa, a recombinant truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors, and PER977 (ciraparantag), a synthetic small molecule that is reported to bind to all of the NOACs.

JW Eikelboon et al., Circ 2015; 132:2412 – ESC Rome, 2016 Sept

2c). Idarucizumab & Other Reversal Agents

Idarucizumab for Dabigatran ReversalFull Cohort Analysis

We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100%. In emergency situations, idarucizumab rapidly, durably, and safely reversed the AC effect of dabigatran.

CV Pollack et al., N Engl J Med 2017; 377:431

Key Measurements Before And After The Administration of Idarucizumab

CV Pollack et. al. N Engl J Med 2017;377:431









Main Cardiac Targets of The Different Domains Of AF Management

P Kirchhof. Lancet 2017;390:1873

J Am Coll Cardiol 2016;68:1929,J Am Coll Cardiol 2017;70:542, J Am Coll Cardiol 2017;69:1247, J Am Coll Cardiol 2017;69:1257

1a). Cumulative Hazard Rates Of Embolic Events According To The Pattern Of AF Occurrence

T Vanassche, SJ Connolly et. al. Eur Heart J. 2015;36:281

1b). CHA2DS2-VASc (Recurrent AF) in Predicting Clinical Outcomes in AF After Catheter Ablation

T-F Chao et al., JACC 2011; 58:2380 (Japan) – 565 Pts

1c). AF Burden - After Catheter AblationSeveral Strategies (Linq Recorder etc)

EI Charitos et. al. Circulation. 2012;126:806 (Luebeck, Germ.)

KC Koskinas et. al. J AmColl Cardiol Intv 2016;9:1374

2a) Bleeding Risk, Ischemic Stroke Risk, Indications for Left Atrial Appendage Closure

PROTECT AF - VY Reddy et. al. JAMA. 2014;312(19):1988- RP Whitlock et. al. Circulation. 2015;131:756

2b). Primary Efficacy Outcome of Watchman LAA Closure For Embolic Protection In AF PROTECT

AF Over 60 Months

2c). Stroke Prevention in AF With LAA Closure

PREVAIL and PROTECT AF (VY Reddy et. al.) J Am Coll Cardiol 2017;70:2964









Screening for Atrial Fibrillation

B Freedman et. al. Circulation. 2017;135:1851









ACC New York, Dec 9, 2017 No Disclosures

Atrial Fibrillation 2017 - 2018Quality of Life and Preventing Stroke

The 14 Clinical Challenges

Presenter

Presentation Notes

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Atrial Fibrillation 2017 -2018 Quality of Life and .../media/Non-Clinical/Files-PDFs-Excel-MS-Word … · PIONEER AF-PCI (CM Gibson et. al. ) NEJM 2016;375:2423 Group 3 - D-adjusted